Isolates or "strains" of scrapie prions possess and retain distinct phenotypes when serially passaged in a given species. The information for their distinct, inherited traits must be contained within the infectious prion particle yet there is no evidence, to date, for a scrapie specific nucleic acid. The existence of these isolates constitutes a touchstone for any model of prion replication and structure. The goal of this proposal is to compare two distinct isolates of hamster scrapie prions in cultured cells. These isolates, designated Sc237 and 139H, differ dramatically in their incubation times in Syrian hamsters. The Sc237 isolate causes in about 70 days while the 139H isolate cause disease in about 150 days. Using SH cells, a novel prion-infectible hamster cell line, the "genetics" of these two isolates will be studied by experiments designed to assess their stability in tissue culture, the appearance of mutations, and phenotypical mixing. The biochemical characteristics of the PrPSc synthesized in SH cells infected with each isolate will be compared. The proposed study may begin to unravel biological and molecular differences between these isolates and thus begin to clarify the concept of scrapie prion "strains".